tbuckley/cabot-search huggingface dataset:
Venetoclax combined with cladribine in patients with relapsed/refractory (R/R) T-cell prolymphocytic leukemia (T-PLL).
Authors: Naszrin Arani, Nadya Jammal, Alexis Geppner, Kunhwa Kim, Gautam Borthakur, Nitin Jain, Marina Konopleva, Guillermo Garcia-Manero, Alessandra Ferrajoli, Elias Jabbour, Hagop M. Kantarjian, Tapan M. Kadia
Journal: Journal of Clinical Oncology (2022)

e19087 Background: T-cell prolymphocytic leukemia (T-PLL) is an ultra-rare and aggressive mature T-cell leukemia associated with a poor prognosis. First-line therapy is with CD52 monoclonal antibody alemtuzumab and allogenic stem cell transplant (SCT), but treatment is rarely curative. There is a critical need for more active therapies to improve outcomes. The BCL-2 inhibitor venetoclax (VEN) has demonstrated activity in T-PLL. We studied a combination of cladribine plus VEN in 5 patients (pts) with R/R T-PLL to investigate the safety and efficacy of this combination. Methods: We retrospectively analyzed pts ≥ 18 years with R/R T-PLL treated with a backbone of cladribine 5 mg/m 2 intravenous (IV) for 5 days with VEN at a target dose of 600-800 mg orally daily (reduced for concomitant drug interactions) on a 28-day cycle. Two pts concomitantly received alemtuzumab, 1 received ruxolitinib, and 2 pts received both. Baseline demographics, cytogenetics and mutations were collected and summarized using descriptive statistics. Response criteria were defined according to the T-PLL consortium and survival analyzed by Kaplan-Meier method. Results: Five pts with a median age of 64 years (range, 59-66) were treated with cladribine + VEN. Pts had a median of 1 prior therapy (range, 1-3), including 3 (60%) with prior SCT. Overall response rate was 100%, including 2 (40%) complete remission with incomplete count recovery (CRi) (with 1 MRD negative CR), and 3 (60%) partial response (PR). A median of 2 cycles were given (range, 1-4). Baseline characteristics are summarized in Table. All five pts had abnormalities of chromosomes 8, 14, and TCL-1 (positive by FISH); 3 had a STAT5B mutation and 1 each had mutations in JAK1, JAK3, and IL7R. Pts had rapid reductions in all T-PLL-related symptoms and signs (i.e., WBC, splenomegaly, effusions, skin lesions, nodes) within the 2 weeks of starting. The regimen was well-tolerated. Two pts had transient grade 1 creatinine elevations and 4 had grade 4 neutropenia that returned to baseline in a median of 67 days (range, 2-93 days). At the time of data review, 1 patient was alive at 8.3 months. The median overall survival (OS) was 5.8 months. Conclusions: The combination of cladribine and VEN in patients with T-PLL refractory to first-line alemtuzumab was well-tolerated and effective. It was associated with rapid disease control, including splenomegaly, fatigue, pleural infiltrates, and skin infiltration. Staging studies to be presented. This encouraging experience should prompt further study as salvage therapy for T-PLL.[Table: see text]
Association of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Coffee Consumption With All-Cause and Cause-Specific Mortality
Authors: Dan Liu, Zhi-Hao Li, Dong Shen, Pei-Dong Zhang, Wei-Qi Song, Wen-Ting Zhang, Qing-Mei Huang, Pei-Liang Chen, Xi-Ru Zhang, Chen Mao
Journal: Annals of Internal Medicine (2022)

Background: Previous observational studies have suggested an association between coffee intake and reduced risk for death, but these studies did not distinguish between coffee consumed with sugar or artificial sweeteners and coffee consumed without. Objective: To evaluate the associations of consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee with all-cause and cause-specific mortality. Design: Prospective cohort study. Setting: Data were extracted from the UK Biobank. Participants: A total of 171 616 participants (mean age, 55.6 years [SD, 7.9]) without cardiovascular disease (CVD) or cancer at baseline were eligible. Baseline demographic, lifestyle, and dietary data from the UK Biobank were used, with follow-up beginning in 2009 and ending in 2018. Measurements: Dietary consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee was self-reported. All-cause, cancer-related, and CVD-related mortality were estimated. Results: During a median follow-up of 7.0 years, 3177 deaths were recorded (including 1725 cancer deaths and 628 CVD deaths). Cox models with penalized splines showed U-shaped associations of unsweetened coffee, sugar-sweetened coffee, and artificially sweetened coffee with mortality. Compared with nonconsumers, consumers of various amounts of unsweetened coffee (>0 to 1.5, >1.5 to 2.5, >2.5 to 3.5, >3.5 to 4.5, and >4.5 drinks/d) had lower risks for all-cause mortality after adjustment for lifestyle, sociodemographic, and clinical factors, with respective hazard ratios of 0.79 (95% CI, 0.70 to 0.90), 0.84 (CI, 0.74 to 0.95), 0.71 (CI, 0.62 to 0.82), 0.71 (CI, 0.60 to 0.84), and 0.77 (CI, 0.65 to 0.91); the respective estimates for consumption of sugar-sweetened coffee were 0.91 (CI, 0.78 to 1.07), 0.69 (CI, 0.57 to 0.84), 0.72 (CI, 0.57 to 0.91), 0.79 (CI, 0.60 to 1.06), and 1.05 (CI, 0.82 to 1.36). The association between artificially sweetened coffee and mortality was less consistent. The association of coffee drinking with mortality from cancer and CVD was largely consistent with that with all-cause mortality. U-shaped associations were also observed for instant, ground, and decaffeinated coffee. Limitation: Exposure assessed at baseline might not capture changes in intake over time. Conclusion: Moderate consumption of unsweetened and sugar-sweetened coffee was associated with lower risk for death. Primary Funding Source: National Natural Science Foundation of China, Young Elite Scientist Sponsorship Program by CAST, and Project Supported by Guangdong Basic and Applied Basic Research Foundation.
Supporting patients with metastatic breast cancer during therapy with cyclin-dependent kinase 4/6 (CDK) inhibitors: A needs assessment.
Authors: Ciara Catherine Maria O'Sullivan, Ginny Jacobs, Domingo Gregorio Perez, Katrina Jackson, Bethany Schowengerdt, Patrice Lazure, Pam McFadden
Journal: Journal of Clinical Oncology (2022)

e13054 Background: Combination therapy with cyclin dependent kinase 4 and 6 inhibitors (CDK4/6i: palbociclib, ribociclib and abemaciclib) and endocrine therapy (ET) has markedly improved treatment of hormone receptor positive (HR+), HER2-negative (-) advanced or metastatic breast cancer (MBC) worldwide.However, data is limited on why patients may discontinue CDK4/6i based therapy and how healthcare providers (HCPs) see their role in educating patients (Px) about side effects and supporting compliance. Objective: This study identifies reasons for suboptimal compliance and early discontinuation of CDK4/6i in US HR+ HER2- MBC Px, with a focus on HCPs and Px educational needs related to on-treatment monitoring, side effects and symptom management. Methods: A sequential mixed-methods design was used; 45-minute phone interviews (n=25) informed the development of an online survey (n=193). Both phases included HCPs comprising medical oncologists (ONCs), oncology registered nurses (RNs), nurse practitioners, and physician assistants (NPs/PAs) in community-based settings. Results: Identified areas of improvement for HCPs included: suboptimal competencies were identified: educating Px adequately regarding potential side effects and engaging them to monitor, report, and address them. Among HCPs surveyed, 26%-48% reported suboptimal knowledge of side effects of specific CDK4/6i [Table]. Interviewees noted that educating Px and setting expectations on potential side effects was critical, but 52% of ONCs reported suboptimal skill doing so. A majority of HCPs (68%-91%) expect Px to be able to report all side effects, with half of ONCs considering compliance with medication entirely Pxs’ responsibility, compared with NPs/PAs and RNs at 16-17%. Conclusions: This study identified areas where HCPs can improve their ability to counsel Px and address concerns that may influence a Px’s decision to prematurely discontinue therapy and should be used to inform future professional development initiatives. [Table: see text]
Letter to the editor: multiple introductions of MPX in Italy from different geographic areas
Authors: Federica Ferraro, Anna Caraglia, Alessia Rapiti, Danilo Cereda, Francesco Vairo, Giovanna Mattei, Francesco Maraglino, Giovanni Rezza
Journal: Eurosurveillance (2022)

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Self-reported efficacy and usage of cannabis among patients with cancer within the Minnesota Cannabis Program.
Authors: Dylan M. Zylla, Helen Parsons, Jeanette Y Ziegenfuss, Bruce Lindgren, Susan Park, Anne Hudson Blaes
Journal: Journal of Clinical Oncology (2022)

12122 Background: Patients with cancer are increasingly using cannabis to alleviate symptoms of pain, nausea, insomnia, and appetite loss. Despite the increased popularity of cannabis, little is known about the patterns of use in the cancer population, efficacy in treating symptoms outside of small clinical studies, and out-of-pocket expenses. We assessed self-reported efficacy and patterns of cannabis use from patients with cancer registered with the Minnesota Cannabis Program (MCP). Methods: We conducted an anonymous survey from December 2021-January 2022 of 797 individuals with cancer-associated pain, nausea/vomiting and/or anorexia currently enrolled in the MCP who had purchased a cannabis related product in the preceding three months. The mailed survey included questions about cancer history, cannabis use, and changes in symptoms. We conducted a descriptive analysis to describe patterns of use. Results: 225 individuals responded to the survey after a single mailing for a 28% response rate. 70% reported using cannabis at least once prior to cancer diagnosis. Respondents had diverse cancer diagnoses (breast (24%), lung (14%), colorectal (10%), prostate (9%)) and were more often female (52%), married, (71%), white (95%), and retired (40%) with a median age of 62.0. Most respondents (46%) had stage IV disease with the remaining 34% stage 1-3 (20% unknown). Household income varied across respondents with 10% reporting annual income &lt;$20,000, 39% between $50-100k, and 33% with incomes ≥100k. 88% purchased at least one product with THC:CBD (tetrahydrocannabinol/cannabidiol) composition &gt;1. Respondents reported that oral products were preferred to vaporizers (81% vs 45%) and 75% reported at least daily use. 27% reported monthly average out of pocket expenses for cannabis of $100-200; with 31% spending ≥$200/mo. The Table outlines perceived change in symptoms amongst users. Conclusions: Patients with cancer in the MCP with recent cannabis purchases predominantly use high THC:CBD products delivered via oral or vaporizer route on daily basis. While out of pocket costs for these products can be significant, many respondents report significant improvements in cancer related symptoms.[Table: see text]
Impact of high-dose melphalan followed by autologous stem cell transplant in producing MRD negative complete response in newly diagnosed multiple myeloma.
Authors: Mohammad Ebraheem, Joselle Cook, Shaji Kumar, Dragan Jevremovic, Angela Dispenzieri, David Dingli, Francis Buadi, Prashant Kapoor, Martha Lacy, Taxiarchis Kourelis, Rahma M. Warsame, Moritz Binder, Eli Muchtar, Suzanne R. Hayman, Ronald S. Go, Nelson Leung, S. Vincent Rajkumar, Robert A. Kyle, Wilson I. Gonsalves, Morie A. Gertz
Journal: Journal of Clinical Oncology (2022)

e20001 Background: High dose melphalan followed by autologous stem cell transplant (HDM-ASCT) remains the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM) despite advances in treatments. Achievement of complete response (CR) is associated with improved overall survival (OS) and progression-free survival (PFS); Minimal Residual Disease (MRD) negativity (-) using next generation flow cytometry with a sensitivity of 10 -5 is strongly associated with improved PFS and OS. We investigated the rates of conversion to MRD(-), especially MRD(-) CR following HDM-ASCT in patients with NDMM. Methods: We retrospectively reviewed patients with NDMM who underwent early HDM-ASCT at Mayo Clinic Rochester from May 2018 to July 2019. Response assessment was conducted after induction and within 100 days post-ASCT based on 2016 IMWG criteria, except for using Mass-Fix instead of immunofixation. MRD was assessed in bone marrow using the established Euro Flow protocol with sensitivity of 10 -5 . The FISH assay was used to risk-stratify patients as high-risk (HR) and standard risk (SR) cytogenetics as per the mSMART guidelines. Primary outcome measure was the conversion to MRD(-) CR after ASCT. Secondary outcomes include the overall conversion to MRD(-) irrespective of IMWG response, the impact of HR cytogenetics and pre-ASCT IMWG response on conversion to MRD(-) CR. Results: Two-hundred and ten patients were included; 126 (60%) were male and median age 62 years (range 32–77 years). There were 78 (44%) patients with HR cytogenetics. Pre-ASCT, 23 patients (11%) achieved MRD(-) CR, and 66 (31%) patients achieved MRD(-) CR post ASCT. Of 187 patients not in MRD(-) CR pre-ASCT, 45 (24%) converted to MRD(-) CR. Table provides a breakdown of the conversion rate of pre-ASCT IMWG response category to MRD(-) CR post ASCT and patients with MRD(+) CR had the highest rate (78%) of conversion. The presence of HR cytogenetics did not impact rates of MRD(-) CR achievement post ASCT irrespective of pre-ASCT IMWG response (p = 1.0). Overall, irrespective of IMWG response, 43 (20%) patients were MRD(-) pre-ASCT (19 in VGPR, 24 in CR or better) and 102 (49%) patients were MRD(-) post-ASCT (36 in VGPR, 66 in CR or better). Among 85 patients in VGPR post-ASCT, 36 were MRD(-) of which 8 (22%) progressed, while 49 were MRD(+) of which 24 (49%) progressed (p = 0.014). Conclusions: Upfront HDM-ASCT in patients with NDMM leads to deeper responses with 24% converting to MRD(-) CR and more than doubling of the total rate of MRD(-) irrespective of IMWG response. [Table: see text]
Clinical cure vs. a novel trifecta system for evaluating long-term outcomes of minimally-invasive partial or total adrenalectomy for unilateral primary aldosteronism: Results of a multicentric series
Authors: U. Anceschi, M. Mormando, C. Fiori, O. Zappalà, B. De Concilio, A. Brassetti, G. Tuderti, M.C. Ferriero, L. Misuraca, A.M. Bove, R. Mastroianni, A. Carrara, M. Appetecchia, F. Porpiglia, A. Celia, M. Gallucci, G. Tirone, G. Simone
Journal: European Urology (2022)
Robot assisted radical cystectomy with intracorporeal urinary diversion versus open radical cystectomy: Results from the iROC prospective randomised controlled trial
Authors: J.W.F. Catto, J.D. Kelly, P. Khetrapal, G. Ambler, F. Ricciardi, S. Khan, A. Feber, S. Dixon, N. Williams, I. Ahmed, P. Charlesworth, M. Cumberbatch, S. Hussain, A. Noon, S. Kotwal, A. Koupparis, E. Rowe, J. Mcgrath, N.V. Vasdev, C. Brew-Graves, D. Hagan
Journal: European Urology (2022)
Robotic management of surgical complications after robot-assisted radical cystectomy with intracorporeal diversion
Authors: L. Misuraca, R. Mastroianni, G. Tuderti, U. Anceschi, A. Brassetti, M. Ferriero, A.M. Bove, S. Guaglianone, M. Gallucci, G. Simone
Journal: European Urology (2022)
Customized autoantibodies (autoAbs) profiling to predict and monitor immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICI).
Authors: Sofia Genta, Sareh Keshavarzi, Noelle Yee, Alya Heirali, Aaron Richard Hansen, Lillian L. Siu, Samuel Saibil, Lee-Anne Stayner, Maryia Yanekina, Maxwell Sauder, Abdulazeez Salawu, Pavlina Spiliopoulou, Olga Vornicova, Maysa Tamara Silveira Vilbert, Marcus O. Butler, Philippe L. Bedard, Albiruni Ryan Abdul Razak, Bryan Coburn, Andrzej Chruscinski, Anna Spreafico
Journal: Journal of Clinical Oncology (2022)

2528 Background: Using a customized microarray, we previously reported that patients (pts) who develop irAEs grade (G)≥2 and those who do not, have different median fluorescent intensity (MFI) levels of specific autoAbs at baseline (pre-ICI). Leveraging a larger dataset, we evaluated whether overall baseline autoAbs elevation and early increases in autoAbs after ICI can predict irAEs as well as if steroid treatment can reduce autoAbs. Methods: Plasma was obtained from pts receiving ICI in two clinical trials (MET4-IO, NCT03686202 and INSPIRE, NCT02644369) and from healthy controls (hc). Collection time points in MET4-IO and INSPIRE studies included: baseline, 3-4 weeks (w), 6-8 w, 24 w and at the end of treatment and baseline and 6 w respectively. Arrays with 162 autoAg customized for frequent irAEs were incubated with plasma and probed with Abs to detect IgG and IgM reactivity. AutoAbs with MFI &gt;500 per individual were compared between hc and pts with and without irAEs G≥2 by the Student-t test. Results: Samples from 114 pts and 14 hc were analyzed (pts characteristics are summarized in the Table). G≥2 irAEs included: hypothyroidism (13), pneumonitis (10), colitis (7), hepatitis (4), skin toxicity (7), infusion reaction (2), pancreatitis (2), meningitis (1), hypophysitis (1), corneal ulcer (1), high creatinine (1), myocarditis (1), myositis (1), diabetes (1), mucositis (1), myasthenia (1) and adrenal failure (1). Hc had less autoAbs with MFI &gt;500 as compared to pts at baseline (median 32 vs 62 p&lt;0.001). IgG with MFI &gt;500 were higher at baseline in pts who developed G≥2 irAEs vs those without G≥2 irAEs (median 39 vs 33, p=0.03). In 23 pts with plasma collected at the time of irAEs, we observed a significant increase of autoAbs with MFI&gt;500 from baseline (median 84 vs 77 p= 0.009). Paired samples at the time of irAEs and after steroids were available for 9/23 pts, showing lower autoAbs after steroid treatment (54 vs 79 p=0.006). No differences in autoAbs with MFI&gt;500 pre and post ICI were seen in pts without G≥2 irAEs (baseline vs first post ICI collection median 58 vs 60, p=0.13). Conclusions: We observed a higher number of IgG with MFI &gt;500 at baseline and a greater increase after ICI administration in individuals with irAEs compared to those without irAEs. Steroid treatment resulted in a decrease in autoAbs. A prospective study is ongoing to validate the potential role of autoAbs for risk stratification and monitoring of irAEs. [Table: see text]
Clinical utility of a molecular tumor board (MTB) in a community oncology practice.
Authors: Thomas Amatruda, Nithya Malisetti, Jeff Hirst, Malia Vadnais, Rajini Katipamula-Malisetti
Journal: Journal of Clinical Oncology (2022)

e15038 Background: We convened a molecular tumor board in an oncology specialty practice of 60 oncologists. Monthly meetings were held remotely, with participation of molecular oncology experts from Caris Life Sciences. Cases were selected for MTB by CLS or clinicians, largely from patients whose genomic testing results did not suggest level 1 guideline therapy options. Methods: We reviewed the clinical value of the genomic test results. To measure the impact of the MTB on patient care, we reviewed a sample of cases with a database instrument. Results: Over calendar year 2021, 491 genomic tests were reported by CLS. These tests involved whole exome and whole transcriptome analysis of microdissected tumor samples. 151 tests showed no association with approved therapy on initial report. In addition to the reported analysis of mutations and fusions, supplemental data concerning emerging biomarkers such as deletions, homologous repair deficiency, and gene expression was provided by CLS for MTB discussion. Between May 2020 and February 2021, 47 cases were presented, representing 19 different diagnoses. 17 cases were reviewed in detail. In 88% of cases (15/17) a recommendation was made by the group. These included suggestions for standard therapy, on sequencing of therapies, on genetic counseling and testing for inherited mutations, and on clinical trial opportunities for emerging biomarker guided therapeutics. In 35% of cases (6/17), the tumor board presentation had an impact on care. In 17% of cases (6/17), we suggested germline genetic testing for patient or family. In 23% of cases (4/17), patient treatment was changed based on discussion. In 9 cases, recommendations were not acted on, because patients deteriorated, remained stable, or chose other therapies. Many patients were presented after multiple lines of treatment or at a time of declining clinical status, which limited the clinical impact of MTB discussion. Evaluation of inherited mutations in patients and family members were difficult to complete when care was dispersed across multiple health systems. Conclusions: The MTB provided valuable updates on new molecular findings and targeted therapies. Incorporation of tumor genomic testing and MTB discussion at an earlier point in the clinical care continuum could improve overall patient outcomes. Challenges in the structure and utility of the conference will be discussed.
Laparoscopic management of xanthogranulomatous pyelonephritis: Comparison of two different yet similar cases
Authors: C. Laranjo Tinoco, A. Cardoso, R. Matos Rodrigues, S. Anacleto, A.S. Araújo, M. Cerqueira Alves, E. Carvalho-Dias
Journal: European Urology (2022)
Nutritional and Metabolic Control of Ferroptosis
Authors: Eikan Mishima, Marcus Conrad
Journal: Annual Review of Nutrition (2022)

Ferroptosis is a type of regulated cell death characterized by an excessive lipid peroxidation of cellular membranes caused by the disruption of the antioxidant defense system and/or an imbalanced cellular metabolism. Ferroptosis differentiates from other forms of regulated cell death in that several metabolic pathways and nutritional aspects, including endogenous antioxidants (such as coenzyme Q10, vitamin E, and di/tetrahydrobiopterin), iron handling, energy sensing, selenium utilization, amino acids, and fatty acids, directly regulate the cells' sensitivity to lipid peroxidation and ferroptosis. As hallmarks of ferroptosis have been documented in a variety of diseases, including neurodegeneration, acute organ injury, and therapy-resistant tumors, the modulation of ferroptosis using pharmacological tools or by metabolic reprogramming holds great potential for the treatment of ferroptosis-associated diseases and cancer therapy. Hence, this review focuses on the regulation of ferroptosis by metabolic and nutritional cues and discusses the potential of nutritional interventions for therapy by targeting ferroptosis.